Article Text
PDF
Statistics from Altmetric.com
Tirzepatide for the treatment of obstructive sleep apnoea and obesity
There are no licensed pharmacological treatments for obstructive sleep apnoea (OSA). Obesity is a modifiable risk factor for OSA with existing pharmacological interventions. One such treatment is tirzepatide which is a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide-1 (GLP-1) receptor agonist. Malhotra et al. (N Engl J Med 2024;391:1193–1205) reported the SURMONT-OSA phase three trials which evaluated the safety and efficacy of tirzepatide for the treatment of OSA in obese adults. SURMONT-OSA comprised of two multi-centre, international, double-blind, randomised, controlled trials conducted over 52 weeks. All participants had moderate-severe OSA. Participants were randomised to placebo or tirzepatide treatment arms. Trial one included participants unable or unwilling to use positive airway pressure (PAP) therapy (n=234) and trial two included participants using and continuing PAP therapy (n=235). The primary end-point was the change in apnoea-hypopnea index (AHI) from baseline. In trial one the mean change in AHI at week 52 was −25.3 events/hour (95% CI, −29.3 to −21.2) with tirzepatide and −5.3 events/hour (95% CI, −9.4 to −1.1) with placebo. In trial 2, after withdrawing PAP therapy, the mean change in AHI at week 52 with tirzepatide was −29.3 events/hour (95% CI, −33.2 to −25.4, p<0.001) and −5.5 events/hour (95% CI, −9.9 to −1.2, p<0.001) with placebo. In each trial tirzepatide produced a statistically significant (p<0.001) difference in AHI. In trials 1 and 2 tirzepatide markedly attenuated but did not abolish the AHI (55% and 62% reductions respectively). Participants who received tirzepatide had significant reductions in systolic blood pressure, CRP and body weight. There was no difference in reported adverse events but there were two cases of acute pancreatitis in tirzepatide groups. The authors concluded that tirzepatide is a safe and effective treatment for OSA in obese patients with the potential to also improve cardiovascular and mortality outcomes. Further work, including head-to-head comparisons with CPAP, is needed before tirzepatide could be considered a first-line therapy.
Long-term oxygen therapy for 24 or 15 hours per day in severe hypoxemia
Long-term oxygen therapy (LTOT) is well-established to improve survival in patients with severe resting hypoxaemia. Current recommendations suggest at least 15hours of usage per day. The REDOX trial (N Engl J Med 2024;391:977–988) tested the hypothesis that LTOT for 24hours does not provide benefit above 15hours per day therapy. This randomised controlled trial took place across multiple centres in Sweden. The trial used the Swedish National Registry for Respiratory Failure to randomly assign patients to 24hours (n=117) or 15hours (n=124) per day LTOT. The primary outcome was hospitalisation or death from any cause within 1 year. The results showed that risk of hospitalisation or death within 1 year was not lower in the 24hour group compared with the 15hour group (mean rate, 124.7 and 124.5 events per 100 person-years, respectively; HR, 0.99; 95% CI, 0.72 to 1.36). This study supports findings from previous observational data from Sweden that using LTOT for 24 hours a day does not provide meaningful benefits over 15 hours a day usage.
CPAP may promote an endothelial inflammatory milieu in sleep apnoea after coronary revascularization
CPAP increases circulating levels of angiopoietin-2 (Ang-2), a lung distension-responsive proangiogenic factor which promotes endothelial inflammation. Peker et al. (Lancet EBioMedicine. 2024 Mar;101:105015) aimed to investigate if CPAP modifies Ang-2 levels in patients with OSA and cardiovascular disease. This study involved a secondary analysis of samples from the RICCADSA trial which was a single-centre randomised controlled trial conducted in Sweden between 2005 and 2010. Patients with coronary artery disease who underwent revascularisation within 6 months were screened for OSA. A total of 189 patients with moderate-severe OSA were then randomised to receive CPAP (n=91) or usual care (n=98). This current study examined the change in Ang-2 levels from baseline to 12 month follow-up. Results were compared with patients without OSA undergoing revascularisation to assess natural trends in Ang-2 levels (n=91). Several other biomarkers for endothelial and lung epithelial function were measured across all groups. The results show that after 12 months levels of Ang-2 declined in the usual care group in line with non-OSA trends. Contrastingly, in the CPAP group, circulating levels of Ang-2 failed to decline compared with baseline. The change in Ang-2 levels from baseline to 12 months was significantly different between CPAP and usual care group (median difference = −0.32, 95% CI −0.57,–0.06, p=0.018). Greater Ang-2 levels were associated with greater median CPAP pressure (p=0.039) but not with hours of CPAP use (p=0.34). Furthermore, increased level of Ang-2 from baseline to 12 months were associated with mortality in patients with OSA after revascularisation on linear cox regression. The authors suggest that CPAP may alter the natural trend of Ang-2 following revascularisation in a pattern which is associated with worse cardiovascular outcomes. Further investigation is required given the exploratory nature of this study.
Combination pharmacological therapy targeting multiple mechanisms of sleep apnoea: a randomised controlled cross-over trial
AtoOxy is a combination drug containing noradrenergic atomoxetine and antimuscarinic oxybutynin. A small randomised controlled trial has suggested that AtoOxy improves pharyngeal muscle responsiveness and reduces AHI by 60%. Acetazolamide, a carbonic anhydrase inhibitor, has also been demonstrated to reduce AHI by approximately 33% by modifying loop gain. Sands et al. (Thorax. 2024 Feb 15;79(3):259–268) aimed to evaluate if combining AtoOxy and acetazolamide before bedtime reduces AHI more compared with AtoOxy or acetazolamide alone in patients with moderate-severe OSA. Nineteen participants were recruited to this cross -over, double blind, randomised, controlled trial which took place at two sites (Brigham and Womens Hospital, Boston and Monash University, Melbourne). The results showed that AtoOxy-plus-acetazolamide did not lower the AHI more than AtoOxy alone (difference in change from baseline of+2% (95% CI,−11 to 18, p=0.8)). All three active intervention groups lowered the AHI from baseline more than placebo: AtoOxy −49% (95% CI, −62 to –33, p=3×10–6), AtoOxy-plus-acetazolamide −47% (95% CI, −61 to 31, p=8×10–6) and acetazolamide −34% (95% CI, 14 to 50, p=0.002). The authors conclude that the physiological mechanisms for AtoOxy and acetazolamide overlap.
Ethics statements
Patient consent for publication
Footnotes
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.